title: Immune evasion of Enterococcus faecalis by an extracellular gelatinase that cleaves C3 and iC3b.
abstract: Enterococcus faecalis (Ef) accounts for most cases of enterococcal bacteremia, which is one of the principal causes of nosocomial bloodstream infections (BSI). Among several virulence factors associated with the pathogenesis of Ef, an extracellular gelatinase (GelE) has been known to be the most common factor, although its virulence mechanisms, especially in association with human BSI, have yet to be demonstrated. In this study, we describe the complement resistance mechanism of Ef mediated by GelE. Using purified GelE, we determined that it cleaved the C3 occurring in human serum into a C3b-like molecule, which was inactivated rapidly via reaction with water. This C3 convertase-like activity of GelE was shown to result in a consumption of C3 and thus inhibited the activation of the complement system. Also, GelE was confirmed to degrade an iC3b that was deposited on the Ag surfaces without affecting the bound C3b. This proteolytic effect of GelE against the major complement opsonin resulted in a substantial reduction in Ef phagocytosis by human polymorphonuclear leukocytes. In addition, we verified that the action of GelE against C3, which is a central component of the complement cascade, was human specific. Taken together, it was suggested that GelE may represent a promising molecule for targeting human BSI associated with Ef.
authors.affiliation: Department of Biotechnology, Hoseo University, Asan City, Chungnam, South Korea.
authors.forename: Shin Yong
authors.initials: SY
authors.lastname: Park
authors.forename: Yong Pyo
authors.initials: YP
authors.lastname: Shin
authors.forename: Chong Han
authors.initials: CH
authors.lastname: Kim
authors.forename: Ho Jin
authors.initials: HJ
authors.lastname: Park
authors.forename: Yeon Sun
authors.initials: YS
authors.lastname: Seong
authors.forename: Byung Sam
authors.initials: BS
authors.lastname: Kim
authors.forename: Sook Jae
authors.initials: SJ
authors.lastname: Seo
authors.forename: In Hee
authors.initials: IH
authors.lastname: Lee
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001770:Blood Bactericidal Activity / Q000276:immunology; D002645:Chickens; D003167:Complement Activation / Q000276:immunology; D003176:Complement C3 / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology; D003179:Complement C3b / Q000037:antagonists & inhibitors / Q000378:metabolism*; D003170:Complement Pathway, Alternative / Q000276:immunology; D004285:Dogs; D013293:Enterococcus faecalis / Q000201:enzymology* / Q000276:immunology*; D045604:Extracellular Fluid / Q000201:enzymology* / Q000276:immunology; D018093:Gelatinases / Q000502:physiology*; D016908:Gram-Positive Bacterial Infections / Q000201:enzymology / Q000276:immunology / Q000382:microbiology; D006168:Guinea Pigs; D006801:Humans; D006868:Hydrolysis; D051379:Mice; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000276:immunology; D010587:Phagocytosis / Q000276:immunology
chemical_list: D003176:Complement C3; D003179:Complement C3b; D018093:Gelatinases